OVERVIEW. Project Summary. This renewal application of a basic research Conte Center aims to elucidate the neurobiological mechanisms for social decision-making in humans. While our current Conte Center investigated the basic systems for decision-making, and did so in both humans and monkeys, this renewal now focuses only on humans, and on more translationally relevant questions. In particular, we now focus on how social inference and context come into play. How do we attribute internal states, such as values, beliefs, and intentions, to other people? How does this depend on the context in which we observe those other people? How does it influence how we can learn from others, how we make altruistic decisions about them, how we deal with social threat? This set of new questions builds directly on our current Conte Center, and is of critical translational importance for understanding deficits in social decision-making such as those that occur in autism spectrum disorders and other psychiatric illnesses. Three cores provide administrative, neuroimaging, and participant recruitment and assessment resources for five Projects that are each directed by internationally renowned leaders, all of whom have a track record of scientific collaboration, student training, and expertise in the topic of the planned studies. Unique innovative strengths of this application are the combination of neuroimaging, intracranial electrophysiology, and lesion studies in human subjects. Cross-cutting questions can be addressed with this multimodal approach, which includes neuroimaging in the very same subjects from whom we record electrophysiologically, and in lesion subjects. Project 1 begins by investigating how social inference and context guides social learning. Projects 2 and 3 examine how social inference modulates social decision-making, in either prosocial, altruistic contexts (Project 2) or under social threat (Project 3). Project 4 examines these questions in relation to how we represent other people and ourselves, using single-unit recordings. Project 5 focuses on lesion studies of the prefrontal cortex, which is the brain region most closely involved in the processes under investigation. This science is woven into a training and outreach program emphasizing dissemination and diversity; and all data are made available for data sharing. The uniform recruitment and assessment of participants, the tight integration and communication between Projects, and the collaborative track record of the team will leverage these studies to a systematic and coordinated investigation of the largest outstanding questions in social decision-making. Progress on this topic will be an essential component for better diagnoses and treatments for a range of psychiatric disorders, including autism, addiction, and mood disorders.